1. Field of the Invention
The present invention relates to a novel use of a N1-cyclic amine-N5-substituted biguanide derivative in preparing a medicine for preventing or treating fibrosis.
2. Description of the Related Art
Fibrosis is a phenomenon characterized by hardening in part of an organ, and representative examples include pulmonary fibrosis or liver fibrosis. Fibrosis mostly occurs as a consequence of a disturbed damage healing process, after mental trauma or chronic inflammation. Although fibrosis occurs in most organs, in particular, it frequently occurs in the liver, lungs, kidneys, heart, eyes, skin, pancreas, intestine, bone marrow, etc., and more particularly, in the liver, lungs, skin, and kidneys, in general.
These organs share common characteristics of activation of abnormal fibroblasts and accumulation of extracellular matrix (ECM), and these characteristics cause damage to the functions of the organs because normal tissues are replaced by cicatricial tissues.
At present, a representative example of a major mechanism known to induce fibrosis is the epithelial-mesenchymal transition (EMT).
That is, in the case of epithelial or endothelial damage, various inflammatory factors in normal tissues become freed, the blood coagulation process initiates as a process of anti-fibrinolytic-coagulation, and white blood cells are aggregated near the wound area, thereby activating the pericyte-myofibroblast transition. As a result, extracellular matrices (ECM), i.e., myofibroblasts, fibroblasts, and mesenchymal cells, are formed, and collagen fibers regenerate blood vessels and tissues and remove scars, thereby accomplishing normalization. However, continuous stimulation induces excess accumulation of ECM, thus leading to fibrosis (Resident mesenchymal cells and fibrosis, Nicol Hutchison, Cecile Fligny, Jeremy S. Duffield, Biochimica et Biophysica Acta, 2012).
That is, it is known that a cell loses its polarity and changes its shape through the EMT process and thereby inhibits cytokeratins, E-cadherin, and tight junctions, which are epithelial markers, whereas activating vimentin, Snail/Slug, extracellular matrix, matrix metalloproteinase, and α-smooth muscle actin (α-SMA), which are mesenchymal markers, thereby causing fibrosis (Differentiation plasticity regulated by TGF-β family proteins in development and disease, Rik Derynck and Rosemary J. Akhurst, Nature Cell Biology, 9(9), 1000-1004, 2007).